Amide bond formation is one of the most frequently used transformations in organic chemistry. The most desirable amide synthesis, a direct condensation of carboxylic acids with amines, is hindered by the intrinsic acid–base reactivity of the starting materials. The thermal amide bond formation from the ammonium carboxylate salts requires high temperatures, which can be lowered by Lewis acids or boronic acid derivatives. However, even the best known systems are limited to a narrow range of amines and require scavenging the reaction water, for example, by large amounts of molecular sieves. Therefore, amides are usually synthesized by aminolysis of activated carboxylic acid derivatives, such as halides, anhydrides, azides, or activated esters, that are mostly generated in an extra step with aggressive, expensive or waste-intensive reagents. The other main strategy for amide bond formation involves the in situ activation of carboxylic acids by peptide coupling reagents, such as carbodiimides or phosphonium salts. Such amide syntheses are highly optimized and provide access to almost any amide structure in near quantitative yields. In modern protein synthesis, they are complemented by efficient chemical and enzymatic peptide ligation methods. However, the atom economy of all these processes is low, and the cumulative waste generated during amide synthesis is unacceptable. As a result, the ACS GCI Roundtable has identified ‘amide bond formation avoiding poor atom economy’ as the most pressing target for sustainable synthetic method development.